Patch preparation

ABSTRACT

The present invention provides a patch preparation that has an extremely low moisture permeability, has a sufficient ODT effect, is excellent in drug releasability and in anchoring property of its drug-containing pressure-sensitive adhesive layer, and has a preferred patch feeling. The patch preparation of the present invention includes a support; and a pressure-sensitive adhesive layer containing an adherent polymer and a drug on one surface of the support, wherein: the support has a polyester base layer, an inorganic oxide layer, and a polyester nonwoven fabric layer in the stated order; the polyester base layer has a thickness of 1.0 μm to 16 μm; and the pressure-sensitive adhesive layer is laminated on the polyester nonwoven fabric layer.

This application claims priority under 35 U.S.C. Section 119 to JapanesePatent Application No. 2011-158586 filed on Jul. 20, 2011 and JapanesePatent Application No. 2012-148212 filed on Jul. 2, 2012, which areherein incorporated by reference.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to a patch preparation having a supportcontaining an inorganic oxide layer and a pressure-sensitive adhesivelayer containing a drug.

2. Description of the Related Art

In recent years, a transdermal absorption-type patch preparation thatdelivers a drug into a living organism by being applied to a skinsurface has been developed. The patch preparation has been attractingattention because of such an excellent advantage as described below. Thepatch preparation can maintain a plasma drug concentration within aneffective therapeutic range for a long time period, can be easilyapplied, or can avoid a first liver pass effect. With regard to suchpatch preparation, the realization of a preparation that exerts asufficient drug effect with a small preparation area or in a short patchtime is expected to lead to an improvement in quality of life (QOL) of apatient. The realization of such preparation requires an improvement indrug releasability. The drug releasability of a patch preparation can begenerally improved by such means as the increase of a drug concentrationin the patch preparation or the addition of an absorption enhancer.However, such means may adversely affect the physical properties anddrug stability of the patch preparation (or its drug-containingpressure-sensitive adhesive layer), and concerns are rising that ittakes a considerable time period and a considerable cost to establishmeans for solving the problem.

A technology for improving the drug releasability by means of anocclusive dressing technique (ODT) effect has been proposed to avoidsuch problem as described above. Such technology basically involvesmaking the patch preparation lowly moisture-permeable. For example,Japanese Patent Application Laid-open No. Hei 4-244019 describes thatdrug releasability is improved with the ODT effect caused by covering asupport with a covering material that can be easily released and islowly moisture-permeable. The technology described in Japanese PatentApplication Laid-open No. Hei 4-244019 realizes the low moisturepermeability not by making the support lowly moisture-permeable but byusing the lowly moisture-permeable covering material. In addition, U.S.Patent Application Publication No. 2006-0078604 describes a technologyinvolving causing the ODT effect with a lowly moisture-permeable supportto improve drug releasability. The literature describes a single layeror laminate of a specific polymer film as the lowly moisture-permeablesupport (for example, paragraphs 0369 to 0382).

However, a patch preparation described in Japanese Patent ApplicationLaid-open No. Hei 4-244019 is not such that the support itself isresponsible for the low moisture permeability. Although a patchpreparation described in U.S. Patent Application Publication No.2006-0078604 is such that the support itself is responsible for the lowmoisture permeability, the anchoring property of its drug-containingpressure-sensitive adhesive layer has room for improvement. Insufficientanchoring property of the drug-containing pressure-sensitive adhesivelayer may adversely affect its patch property, and hence a situation inwhich an expected effect is not obtained may occur. Therefore, a patchpreparation that can sufficiently utilize the ODT effect and isexcellent in drug releasability, and whose drug-containingpressure-sensitive adhesive layer is excellent in anchoring property hasbeen desired.

SUMMARY OF THE INVENTION

The present invention has been made to solve the conventional problems,and an object of the present invention is to provide a patch preparationthat has an extremely low moisture permeability, has a sufficient ODTeffect, is excellent in drug releasability and in anchoring property ofits drug-containing pressure-sensitive adhesive layer, and has apreferred patch feeling.

The inventors of the present invention have found that the object can beachieved by interposing an extremely thin inorganic oxide layer betweena thin polyester base layer and a polyester nonwoven fabric layer in asupport of a patch preparation. Thus, the inventors of the presentinvention have completed the present invention. Further, the inventorsof the present invention have found the following. The use of thesupport of such construction can impart durability to the inorganicoxide layer, and as a result, the inorganic oxide layer can be favorablyprevented from dropping off owing to bending or friction, and canrealize the excellent flexibility of the patch preparation and theexcellent anchoring property of its drug-containing pressure-sensitiveadhesive layer.

According to the present invention, a patch preparation is provided. Thepatch preparation includes:

a support; and

a pressure-sensitive adhesive layer containing an adherent polymer and adrug on one surface of the support,

wherein:

the support has a polyester base layer, an inorganic oxide layer, and apolyester nonwoven fabric layer in the stated order;

the polyester base layer has a thickness of 1.0 μm to 16 μm; and

the pressure-sensitive adhesive layer is laminated on the polyesternonwoven fabric layer.

In one embodiment of the invention, the inorganic oxide layer has athickness of 1 nm to 300 nm.

In one embodiment of the invention, the patch preparation has a moisturepermeability of 0.1 g/m²⁰·24 h to 80 g/m²⁰·24 h.

In one embodiment of the invention, the adherent polymer comprises anacrylic polymer obtained by copolymerizing a (meth)acrylic acid alkylester and a functional monomer.

In one embodiment of the invention, the pressure-sensitive adhesivelayer has a thickness of 10 μm to 200 μm.

In one embodiment of the invention, the pressure-sensitive adhesivelayer further contains an organic liquid component.

According to the present invention, by interposing an extremely thininorganic oxide layer between a thin polyester base layer and apolyester nonwoven fabric layer in a support of a patch preparation, apatch preparation that has an extremely low moisture permeability, has asufficient ODT effect, and is excellent in drug releasability can beobtained. In addition, the use of the support of such construction canimpart durability to the inorganic oxide layer, and as a result, theinorganic oxide layer can be favorably prevented from dropping off owingto bending or friction. Further, the use of the support of suchconstruction can realize excellent anchoring property of itsdrug-containing pressure-sensitive adhesive layer and provides highflexibility, and hence an excellent patch feeling can be realized. Inaddition, the patch preparation of the present invention isinconspicuous upon its attachment to a skin even when painting or thelike is not performed, and hence an adverse effect caused by a paint orthe like is eliminated. Further, the patch preparation of the presentinvention does not cause any inconvenience even when a user undergoes acheckup such as MRI or CT in a state where the patch preparation isattached to the user.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic sectional view illustrating a patch preparationaccording to a preferred embodiment of the present invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

FIG. 1 is a schematic sectional view illustrating a patch preparationaccording to a preferred embodiment of the present invention. A patchpreparation 100 has a support 10 and a pressure-sensitive adhesive layer20 on one surface of the support 10. The pressure-sensitive adhesivelayer 20 contains an adherent polymer and a drug (substantially containsa pressure-sensitive adhesive containing the adherent polymer and thedrug). The support 10 has a polyester base layer 11, an inorganic oxidelayer 12, and a polyester nonwoven fabric layer 13 in the stated order.Practically, the polyester nonwoven fabric layer 13 is laminated on theinorganic oxide layer 12 through any appropriate adhesive layer (notshown). In the patch preparation 100, the pressure-sensitive adhesivelayer 20 and the polyester nonwoven fabric layer 13 are laminated.Hereinafter, each layer is specifically described.

A. Support

A-1. Polyester Base Layer

A polyester base layer 11 is constituted of a polyester film. Anyappropriate polycondensate of polycarboxylic acid and a polyol can beused as the polyester. Specific examples thereof include polyethyleneterephthalate, polybutylene terephthalate, polyethylene naphthalate,polybutylene naphthalate, a copolymer containing repeating units thereofand any other ester repeating units, and a mixture of those polymers anda polymer formed of other ester repeating units. Examples of thepolycarboxylic acid component forming the any other ester repeatingunits include aromatic dicarboxylic acids such as isophthalic acid,diphenyldicarboxylic acid, diphenyletherdicarboxylic acid,diphenylsulfone dicarboxylic acid, and naphthalene dicarboxylic acid;and aliphatic dicarboxylic acids such as adipic acid and sebacic acid.Examples of the polyol component include alkylene glycols such astrimethylene glycol, tetramethylene glycol, and hexamethylene glycol;aromatic diols such as hydroquinone, resorcin, and bisphenol A;aliphatic diols such as bis(hydroxyethoxyphenyl)sulfone andbis(hydroxyethoxyphenyl)propane; and diethylene glycol. Polyethyleneterephthalate, a copolymer containing ethylene terephthalate repeatingunits and any other ester repeating units, and a mixture of polyethyleneterephthalate and a polymer formed of any other ester repeating unitsare preferred. This is because they are superior in safety (nontoxicity)to a living organism, practicality and general-purpose property.

The polyester base layer 11 preferably has as small a thickness aspossible. Reducing the thickness can alleviate a stimulus caused by asupport edge. Specifically, the thickness is 1.0 μm to 16 μm, preferably1.0 μm to 12 μm, more preferably 1.0 μm to 10 μm, still more preferably1.5 μm to 8.0 μm, particularly preferably 2.0 μm to 6.0 μm. When thethickness is less than 1.0 μm, it is difficult to laminate the layer anda nonwoven fabric to be described later to produce the support of thepresent invention, and the practicality of the patch preparation isinsufficient in some cases. When the thickness exceeds 16 μm, the patchpreparation may cause an uncomfortable feeling (stiff feeling) resultingfrom the rigidity of the polyester when attached to a skin surface.

A-2. Inorganic Oxide Layer

In the present invention, the inorganic oxide layer 12 is providedbetween the polyester base layer 11 and the polyester nonwoven fabriclayer 13. Providing such inorganic oxide layer suppresses the moisturepermeability of the entire support, and as a result, the moisturepermeability of the patch preparation. Thus, the releasability of thedrug can be improved by the so-called ODT effect. Further, its inorganicoxide has transparency enough to be used as a base material for thepatch preparation, and hence the patch preparation is inconspicuous uponits attachment to a skin even when painting or the like is notperformed. As a result, an inconvenience caused by a paint or the likecan be prevented. In addition, unlike a metal, the inorganic oxide doesnot cause any inconvenience even when a user undergoes a checkup such asMRI or CT in a state where the patch preparation is attached to theuser.

The inorganic oxide layer 12 is constituted of any appropriate inorganicoxide as long as such effect as described above is obtained. Specificexamples thereof include aluminum oxide, silicon oxide, titanium oxide,magnesium oxide, and indium oxide. The inorganic oxides may be usedalone or in combination. Of those, aluminum oxide and silicon oxide arepreferred. This is because each of those inorganic oxides hasparticularly high general-purpose property and is excellent intransparency.

The inorganic oxide layer 12 is representatively formed by depositingthe inorganic oxide from the vapor onto the polyester base layer. Theinorganic oxide layer has a thickness of preferably 1 nm to 300 nm, morepreferably 1 nm to 200 nm, still more preferably 1 nm to 100 nm,furthermore preferably 3 nm to 50 nm, still further more preferably 5 nmto 20 nm, particularly preferably 7 nm to 12 nm. As long as thethickness of the inorganic oxide layer falls within such range, theextent to which the patch preparation is conspicuous at the time of itsattachment can be additionally alleviated while its low moisturepermeability is maintained. Further, despite the fact that the layer isinterposed between the polyester base layer and the polyester nonwovenfabric layer, adhesiveness between those layers can be sufficientlysecured.

A-3. Polyester Nonwoven Fabric Layer

The polyester nonwoven fabric layer 13 is placed so as to be adjacent tothe pressure-sensitive adhesive layer 20. The polyester nonwoven fabriclayer is constituted of any appropriate polyester nonwoven fabric.Examples of the polyester constituting the nonwoven fabric include thepolyesters described in the section A-1 for the polyester base layer.The polyester constituting the nonwoven fabric may be of the same kindas, or of a kind different from, that of the polyester constituting thepolyester base layer. The polyester constituting the nonwoven fabric ispreferably of the same kind as that of the polyester constituting thepolyester base layer. This is because the adhesiveness between thepolyester nonwoven fabric layer and the polyester base layer can be madeextremely excellent even when the inorganic oxide layer is interposedtherebetween. It should be noted that the phrase “polyesters are of thesame kind” as used in the specification means that monomers constitutingtheir main repeating units are identical to each other, and thepolyesters may be different from each other in copolymerizable component(for example, any other ester repeating unit), or may be different fromeach other in polymerization degree. The nonwoven fabric can be formedby any appropriate method involving using a polyester fiber. Specificexamples of the method of forming the nonwoven fabric include apapermaking method, a hydroentangling method, a needle-punching method,a spun-bonding method, and a melt-blowing method.

The anchoring property of the pressure-sensitive adhesive layer for thesupport can be significantly improved by placing the polyester nonwovenfabric layer so that the layer may be adjacent to the pressure-sensitiveadhesive layer. This is because of the following reason. As thepolyester nonwoven fabric has polyester fibers irregularly placedtherein and hence its surface unevenness is larger than that of, forexample, a polyester woven fabric or knitted fabric in which polyesterfibers are regularly placed, the pressure-sensitive adhesiveconstituting the pressure-sensitive adhesive layer easily enters theunevenness. Further, the inorganic oxide layer can be protected withboth the polyester nonwoven fabric layer and the pressure-sensitiveadhesive layer by placing the polyester nonwoven fabric layer so thatthe layer may be adjacent to the pressure-sensitive adhesive layer.Accordingly, the inorganic oxide layer can be protected in anadditionally strong fashion, and as a result, the durability of theinorganic oxide layer can be significantly improved. In addition,providing the polyester nonwoven fabric layer enables the support tosecure self-supporting property while maintaining the flexibility of thesupport.

The basis weight (weight per unit area) of the polyester nonwoven fabricis not particularly limited. The basis weight of the nonwoven fabric ispreferably smaller than the basis weight of a nonwoven fabric to begenerally used. With such basis weight, the uncomfortable feeling afterthe attachment to the skin surface can be alleviated. Specifically, thebasis weight of the nonwoven fabric is preferably 5 g/m² to 25 g/m²,more preferably 5 g/m² to 20 g/m², still more preferably 8 g/m² to 20g/m². When the basis weight is less than 5 g/m², the anchoring property(anchor effect) between the support and the pressure-sensitive adhesivelayer is not sufficiently improved in some cases. When the basis weightexceeds 25 g/m², an uncomfortable feeling may be caused by the nonwovenfabric at the time of the attachment to the skin.

B. Pressure-Sensitive Adhesive Layer

The pressure-sensitive adhesive layer 20 contains the pressure-sensitiveadhesive containing the adherent polymer and the drug. Thepressure-sensitive adhesive to be used in the pressure-sensitiveadhesive layer is not particularly limited. Specific examples of thepressure-sensitive adhesive include an acrylic pressure-sensitiveadhesive containing an acrylic polymer; a silicone-basedpressure-sensitive adhesive such as a silicone rubber, adimethylsiloxane base, or a diphenylsiloxane base; a rubber-basedpressure-sensitive adhesive such as a styrene-diene-styrene blockcopolymer (such as a styrene-isoprene-styrene block copolymer or astyrene-butadiene-styrene block copolymer), a polyisoprene, apolyisobutylene, or a polybutadiene; a vinyl ether-basedpressure-sensitive adhesive such as polyvinyl methyl ether, polyvinylethyl ether, or polyvinyl isobutyl ether; a vinyl ester-basedpressure-sensitive adhesive such as a vinyl acetate-ethylene copolymer;and a polyester-based pressure-sensitive adhesive formed of a carboxylicacid component such as dimethyl terephthalate, dimethyl isophthalate, ordimethylphthalate and a polyhydric alcohol component such as ethyleneglycol. One kind of those pressure-sensitive adhesives may be usedalone, or two or more kinds thereof may be used in combination. Anonaqueous pressure-sensitive adhesive layer is preferred from theviewpoint of skin adhesion, and hence a hydrophobic pressure-sensitiveadhesive is preferred. The term “nonaqueous pressure-sensitive adhesivelayer” as used herein is not strictly limited to one containing nomoisture but comprehends a pressure-sensitive adhesive layer containinga slight amount of moisture derived from air humidity, the skin, or thelike.

In one embodiment, the pressure-sensitive adhesive layer (substantiallythe pressure-sensitive adhesive) contains an acrylic polymer as theadherent polymer. According to the present invention, as describedabove, the moisture permeability can be suppressed with the support inan extremely favorable fashion. Accordingly, a large number ofadvantages of the acrylic polymer can be effectively exploited while aproblem of the acrylic polymer, i.e., its relatively large moisturepermeability is solved. The acrylic polymer preferably has adherence atnormal temperature (for example, 25° C.). Such acrylic polymer ispreferably an acrylic polymer obtained by copolymerizing a (meth)acrylicacid alkyl ester and a functional monomer, and is more preferably anacrylic polymer obtained by copolymerizing the (meth)acrylic acid alkylester as a main component with the functional monomer. The term “maincomponent” as used herein means a monomer whose content is 50 wt % ormore on the basis of the total weight of all monomers constituting thecopolymer.

As the (meth)acrylic acid alkyl ester (which may hereinafter be referredto as “main monomer”) in the acrylic polymer, any appropriate(meth)acrylic acid alkyl ester may be used. Representative examplesthereof include (meth)acrylic acid alkyl esters, the alkyl group ofwhich is a linear or branched alkyl group having 4 to 13 carbon atoms(for example, butyl, pentyl, hexyl, heptyl, octyl, 2-ethylhexyl, nonyl,decyl, undecyl, dodecyl, or tridecyl). The (meth)acrylic acid alkylester may be used alone or in combination of two or more kinds.

The term “functional monomer” as used in the specification means amonomer having at least one unsaturated double bond which is involved ina copolymerization reaction in its molecule, and having a functionalgroup in its side chain. Specific examples of the functional monomerinclude a carboxylic group-containing monomer such as (meth)acrylicacid, itaconic acid, maleic acid, or maleic acid anhydride; a hydroxylgroup-containing monomer such as a (meth)acrylic acid hydroxyethyl esteror a (meth)acrylic acid hydroxypropyl ester; a sulfoxyl group-containingmonomer such as styrenesulfonic acid, allylsulfonic acid, sulfopropyl(meth)acrylate, (meth)acryloyloxynaphthalene sulfonic acid, oracrylamide methylpropane sulfonic acid; an amino group-containingmonomer such as a (meth)acrylic acid aminoethyl ester, a (meth)acrylicacid dimethylaminoethyl ester, or a (meth)acrylic acidtert-butylaminoethyl ester; an amide group-containing monomer such as(meth)acrylamide, dimethyl (meth)acrylamide, N-methylol(meth)acrylamide, N-methylol propane (meth)acrylamide, or N-vinylacetamide; and an alkoxyl group-containing monomer such as a(meth)acrylic acid methoxyethyl ester, a (meth)acrylic acid ethoxyethylester, a (meth)acrylic acid methoxyethylene glycol ester, a(meth)acrylic acid methoxy diethylene glycol ester, a (meth)acrylic acidmethoxypolyethylene glycol ester, a (meth)acrylic acid methoxypolypreneglycol ester, or a (meth)acrylic acid tetrahydrofuryl ester. Thefunctional monomer may be used alone or in combination of two or morekinds. Of those, in view of pressure-sensitive adherence, cohesiveness,or the like of the pressure-sensitive adhesive layer, the carboxygroup-containing monomer is preferred, and (meth)acrylic acid is morepreferred.

As the acrylic polymer, an acrylic polymer obtained by copolymerizing amain monomer, a functional monomer, and any other monomer may be used.Examples of the any other monomer include (meth)acrylonitrile, vinylacetate, vinyl propionate, N-vinyl-2-pyrrolidone, methyl vinylpyrrolidone, vinyl pyridine, vinylpiperidone, vinylpyrimidine,vinylpiperazine, vinylpyrrole, vinyl imidazole, vinyl caprolactam, andvinyloxazole. The any other monomer may be used alone or in combinationof two or more kinds.

Examples of the particularly preferred acrylic polymer in the presentinvention include a copolymer of acrylic acid 2-ethylhexyl ester/acrylicacid, a copolymer of acrylic acid 2-ethylhexyl ester/acrylicacid/N-vinyl-2-pyrrolidone, and a copolymer of acrylic acid 2-ethylhexylester/acrylic acid 2-hydroxyethyl ester/vinyl acetate. The copolymer ofacrylic acid 2-ethylhexyl ester/acrylic acid and the copolymer ofacrylic acid 2-ethylhexyl ester/acrylic acid/N-vinyl-2-pyrrolidone arepreferred.

Copolymerization ratios (usage ratios of the monomers) in the acrylicpolymer are, for example, as follows: the (meth)acrylic acid alkyl ester(main monomer), the functional monomer, and the any other monomer areused at ratios of 50 wt % to 99.9 wt %, 0.1 wt % to 10 wt %, and 0 wt %to 49.9 wt %, respectively with respect to the total weight of themonomers to be used. Adopting such copolymerization ratios provides anacrylic polymer that has good adhesion to a human skin, and can berepeatedly bonded and released with ease.

The acrylic polymer can be obtained by any appropriate polymerizationmethod. For example, the polymer can be obtained by: adding apolymerization initiator (such as benzoyl peroxide or2,2′-azobisisobutyronitrile) to the monomers; and causing the contentsto react with each other in a solvent (such as ethyl acetate) at 50° C.to 70° C. for 5 hours to 48 hours.

The amount of the adherent polymer (such as the acrylic polymer) in thepressure-sensitive adhesive layer is preferably 30 wt % to 70 wt %, morepreferably 40 wt % to 70 wt % on the basis of the total weight of thepressure-sensitive adhesive layer. When the amount of the adherentpolymer falls short of 30 wt %, the internal cohesive strength of thepressure-sensitive adhesive layer may reduce. When the amount of theadherent polymer exceeds 70 wt %, the tack of the pressure-sensitiveadhesive layer may reduce, or the addition amount of an organic liquidcomponent to be described later may be insufficient.

The drug contained in the pressure-sensitive adhesive layer is notparticularly limited. A drug which can be administered to mammals suchas humans through their skin, that is to say, a drug capable oftransdermal absorption is preferred. Specific examples of such druginclude general anesthetics, hypnotics, antiepileptics, antipyreticanalgesics, anti-vertigenous drugs, psychoneurotic agents, centralnervous system agents, antidementia drugs, local anesthetics, skeletalmuscle relaxants, autonomic nervous system agents, spasmolytics,antiparkinson agents, antihistamines, cardiac stimulants, antiarrhythmicagents, diuretics, hypotensive agents, vasoconstrictors, coronaryvasodilators, peripheral vasodilators, antiarteriosclerosis agents,cardiovascular preparations, anapnoics, antitussives and expectorants,hormone preparations, dermatics for purulence, analgesics,anti-itchings, astrigents and anti-inflammatory agents,anti-dermoinfectives, hemostatics, gout suppressants, antidiabeticagents, antineoplastics, antibiotics, chemotherapeutics, narcotics, andsmoking-cessation aids.

The drug can be present in the pressure-sensitive adhesive layer in anamount enough to provide a desired result, e.g., a desired therapeuticresult in the therapy of a disease, a state, or a disability (that is,an effective dose). The term “effective dose of the drug” means, forexample, such a sufficient amount of the drug that the drug is nontoxicbut exerts a selected effect over a specific time period. Such amountcan be easily determined by a person skilled in the art.

The amount of the drug in the pressure-sensitive adhesive layer is notparticularly limited as long as its effect as a drug for transdermalabsorption is satisfied and the adhesion characteristic of thepressure-sensitive adhesive is not impaired. Specifically, the amount ofthe drug is preferably 0.1 wt % to 60 wt %, more preferably 0.5 wt % to40 wt % on the basis of the total weight of the pressure-sensitiveadhesive layer. When the amount of the drug is less than 0.1 wt %, itstherapeutic effect may be insufficient. When the amount of the drug ismore than 60 wt %, the contents of the pressure-sensitive adhesive andany other additive constituting the pressure-sensitive adhesive layerreduce, and hence sufficient skin adhesion may not be obtained. Inaddition, such amount may be economically disadvantageous.

An organic liquid component can be further incorporated into thepressure-sensitive adhesive layer (substantially the pressure-sensitiveadhesive) as required. The use of the organic liquid component enables,for example, the regulation of the adherence and/or the promotion of thetransdermal absorption of the drug. Examples of the organic liquidcomponent include glycols such as ethylene glycol, diethylene glycol,triethylene glycol, propylene glycol, polyethylene glycol, andpolypropylene glycol; oil and fat such as olive oil, castor oil,squalene, and lanolin; organic solvents such as ethyl acetate, ethylalcohol, dimethyldecyl sulfoxide, methyloctyl sulfoxide, dimethylsulfoxide, dimethyl formamide, dimethyl acetamide, dodecyl pyrrolidone,and isosorbitol; liquid surfactants; plasticizers such as diisopropyladipate, phthalic acid ester, diethyl sebacate, triethyl citrate, andacetyl tributyl citrate; hydrocarbons such as liquid paraffin; andesters such as ethoxylated stearyl alcohol, a glycerin fatty acid ester,and a fatty acid ester. The organic liquid component may be used aloneor in combination of two or more kinds.

Preferred examples of the organic liquid component include a fatty acidester, a glycerin fatty acid ester (especially a mono-, di-, ortriglyceride), and acetyl tributyl citrate. Those components each exertan excellent plasticizing action on the pressure-sensitive adhesivelayer. With regard to the fatty acid ester and the glycerin fatty acidester out of those components, a fatty acid ester of a higher fatty acidand a lower monohydric alcohol is preferred from the viewpoints of:maintaining compatibility with the adherent polymer in thepressure-sensitive adhesive layer; and preventing vaporization in aheating step upon preparation of the patch preparation. Examples of thehigher fatty acid include fatty acids each having preferably 12 to 16,more preferably 12 to 14 carbon atoms. Specific examples thereof includelauric acid, myristic acid, and palmitic acid. Examples of the lowermonohydric alcohol include monohydric alcohols each having 1 to 4 carbonatoms. Specific examples thereof include methanol, ethanol, propanol,isopropanol, and butanol.

The amount of the organic liquid component in the pressure-sensitiveadhesive layer (substantially the pressure-sensitive adhesive) ispreferably 10 wt % to 70 wt %, more preferably 20 wt % to 60 wt %, stillmore preferably 30 wt % to 50 wt % on the basis of the total weight ofthe pressure-sensitive adhesive layer. When the amount of the organicliquid component falls short of 10 wt %, keratin peels upon release ofthe patch preparation, which may do damage to the skin. When the amountof the organic liquid component exceeds 70 wt %, the adhesion may beinsufficient.

The pressure-sensitive adhesive layer (substantially thepressure-sensitive adhesive) may further contain any other component tosuch an extent that an effect of the present invention is not impaired.Examples of such any other component include an antioxidant such asascorbic acid, tocopherol acetate, natural vitamin E,dibutylhydroxytoluene, or butylhydroxyanisole, an amine-ketone-based ageresister such as 2,6-tert-butyl-4-methylphenol, an aromatic secondaryamine-based age resister such as N,N′-di-2-naphtyl-p-phenylenediamine, amonophenol-based age resister such as a2,2,4-trimethyl-1,2-dihydroquinoline polymer, a bisphenol-based ageresister such as 2,2′-methylene bis(4-ethyl-6-tert-butylphenol), apolyphenol-based age resister such as 2,5-tert-butylhydroquione, afiller such as kaolin, hydrated silicon dioxide, zinc oxide, or starchacrylate 1000, a softener such as propylene glycol, a polybutene, ormacrogol 1500, a preservative such as benzoic acid, sodium benzoate,chlorhexidine hydrochloride, sorbic acid, methyl paraoxybenzoate, orbutyl paraoxybenzoate, a colorant such as yellow iron oxide, yellowferric oxide, iron sesquioxide, black iron oxide, carbon black, carmine,3-carotene, copper chlorophyll, food blue No. 1, food yellow No. 4, foodred No. 2, or a glycyrrhiza extract, a cooling agent such as fennel oil,d-camphor, dl-camphor, peppermint oil, d-borneol, or l-menthol, and aperfume such as spearmint oil, clove oil, vanillin, bergamot oil, orlavender oil. The kind and amount of the any other component to becontained may be appropriately set depending on purposes.

In the present invention, the pressure-sensitive adhesive layer(substantially a pressure-sensitive adhesive layer-forming composition)may be subjected to a physical cross-linking treatment based on, forexample, radiation irradiation such as UV light irradiation or electronbeam irradiation, or a chemical cross-linking treatment involving usingany one of the various cross-linking agents as required.

Any such cross-linking agent is not particularly limited as long as thecross-linking agent is such that the formation of cross-links is notinhibited by the drug. Specific examples of the cross-linking agentinclude a peroxide (such as benzoyl peroxide (BPO)), a metal oxide (suchas magnesium aluminometasilicate), a polyfunctional isocyanate compound,an organic metal compound (such as zirconium and zinc alaninate, zincacetate, zinc ammonium glycinate, or a titanium compound), a metalalcoholate compound (such as tetraethyltitanate, tetraisopropyltitanate, aluminum isopropylate, or aluminum sec-butylate), and a metalchelate compound (such as titanium dipropoxy bis(acetylacetonate),tetraoctylene glycol titanium, aluminum isopropylate, ethyl acetoacetatealuminum diisopropylate, aluminum tris(ethylacetoacetate), or aluminumtris(acetylacetonate)). The cross-linking agent may be used alone or incombination of two or more kinds. Of those, the polyfunctionalisocyanate compound and the metal chelate compound are preferred. Thisis because those compounds each have high cross-linking efficiency in anacrylic pressure-sensitive adhesive having a carboxyl group.

When the cross-linking agent is used, its usage is preferably 0.01 wt %to 10 wt %, more preferably 0.05 wt % to 5 wt % on the basis of thetotal weight of the pressure-sensitive adhesive layer. When the usage ofthe cross-linking agent is less than 0.01 wt %, the number of cross-linkpoints is so small that a sufficient cohesive strength cannot beimparted to the pressure-sensitive adhesive layer, and hence an adhesiveresidue or a strong skin stimulus resulting from the cohesive failure ofthe layer may occur at the time of the release. When the usage of thecross-linking agent is more than 10 wt %, the cohesive strength is largebut a sufficient skin adhesive strength cannot be obtained in somecases. In addition, a skin stimulus may occur owing to the remaining ofan unreacted cross-linking agent.

The chemical cross-linking treatment can be performed through, forexample, such a step that after the addition of the cross-linking agentto the pressure-sensitive adhesive layer, the pressure-sensitiveadhesive layer is heated to a temperature equal to or more than itscross-linking reaction temperature and then stored, i.e., an aging step.A heating temperature and a heating time are appropriately selecteddepending on the kind of the cross-linking agent. The heatingtemperature is preferably 60° C. to 90° C., more preferably 60° C. to80° C. The heating time is preferably 12 hours to 96 hours, morepreferably 24 hours to 72 hours. The cross-linked pressure-sensitiveadhesive layer containing the organic liquid component is preferredbecause the layer shows a gel state, and hence has moderate skinadhesion and has such cohesiveness as to hardly cause an adhesiveresidue at the time of its release.

C. Patch Preparation

The patch preparation of the present invention is obtained by formingthe pressure-sensitive adhesive layer described in the section B on onesurface of the support described in the section A. The patch preparationof the present invention is provided as a transdermal absorption-typepreparation, and is provided as a matrix-type patch preparation, areservoir-type patch preparation, or the like, in particular, as amatrix-type patch preparation.

The moisture permeability of the patch preparation is preferably 0.1g/m²·24 h to 80 g/m²·24 h, more preferably 0.5 g/m²·24 h to 70 g/m²⁰·24h, still more preferably 1 g/m²⁰·24 h to 60 g/m²⁰·24 h. As long as themoisture permeability of the patch preparation falls within such range,a sufficient ODT effect is obtained and the releasability of the drugcan be improved. According to the present invention, such extremely lowmoisture permeability can be realized while the transparency of theentire patch preparation is maintained. The moisture permeability of thepatch preparation can be controlled by adjusting, for example, thethickness of the inorganic oxide layer of the support, the thickness andmaterial of the polyester base layer, and the thickness, material, andbasis weight of the polyester nonwoven fabric layer. The moisturepermeability can be measured in conformity with JIS L1099.

Practically, the adherent surface of the pressure-sensitive adhesivelayer can be covered with a release liner for protecting the surfacebefore its use. The release liner is not particularly limited. Specificexamples of the release liner include a glassine paper, a polyethylene,a polypropylene, a polyester, a polyethylene terephthalate, apolystyrene, an aluminum film, a polyethylene foam film, and apolypropylene foam film, and a laminated product thereof, asilicone-processed product thereof, and an emboss-processed productthereof. A release liner made of a polyester (especially polyethyleneterephthalate) resin is preferred in terms of barrier property, a price,and the ease with which a material for the liner is selected. Thesurface on the pressure-sensitive adhesive layer side of the releaseliner may be subjected to a surface release treatment in order that therelease liner can be released from the pressure-sensitive adhesive layerwith additional ease.

The release liner preferably has a uniform thickness in consideration ofthe ease of processing and processing accuracy. The thickness of therelease liner is preferably 25 μm to 200 μm, more preferably 50 μm to150 μm from the viewpoints of, for example, the ease with which thepatch preparation is produced, a cost for the release liner, and theportability and operability of the patch preparation.

The patch preparation of the present invention can be produced by anyappropriate method. For example, the following method is given. First,the support is produced. Specifically, the inorganic oxide is depositedfrom the vapor onto the surface of the polyester film. Thus, a laminateof the polyester base layer and the inorganic oxide layer is obtained.Next, the polyester nonwoven fabric is laminated on the inorganic oxidelayer of the laminate. Thus, the support is obtained. The lamination ofthe polyester nonwoven fabric can be performed by, for example, applyingany appropriate adhesive to the inorganic oxide layer side of thelaminate with a gravure coater or the like so that a dry applicationamount may be about 1 to 3 g/m², and crimping the nonwoven fabric whileperforming heating as required. A known adhesive such as apolyester-based, acrylic, vinyl chloride-based, vinyl acetate-based,rubber-based, or urethane-based adhesive can be used as the adhesive.Next, the release liner is prepared, the pressure-sensitive adhesivelayer is laminated on one surface of the release liner, and the supportis laminated on the pressure-sensitive adhesive layer. Thus, a laminatedsheet is obtained. Alternatively, the laminated sheet is obtained by:laminating the pressure-sensitive adhesive layer on the polyesternonwoven fabric layer of the support; and laminating the release lineron the pressure-sensitive adhesive layer. An approach to laminating thesupport and the pressure-sensitive adhesive layer is not particularlylimited. Specific examples thereof include application, bonding, fusion,and welding. The following method is preferably adopted. Apressure-sensitive adhesive containing, for example, the drug, theadherent polymer, and an organic solvent is prepared, and then thepressure-sensitive adhesive is applied onto the release liner or thesupport, followed by the drying and removal of the organic solvent. Theresultant laminated sheet is cut into a predetermined shape. Thus, thepatch preparation is obtained. The patch preparation can be packaged inany appropriate packaging container as desired. A bag or the like madeof a resin film, a metal foil, or a laminated film thereof is typicallyused as the packaging container.

Hereinafter, the present invention is described in more detail by way ofexamples. However, the present invention is not limited to theseexamples. It should be noted that the terms “part (s)” and “%” in theexamples refer to “part (s) by weight” and “wt %,” respectively unlessotherwise stated.

<Preparation of Support>

Support A: A polyethylene terephthalate (PET) film having a thickness of4 μm was used.

Support B: Aluminum oxide was deposited from the vapor onto one surfaceof the support A so as to have a thickness of 10 nm.

Support C: A PET nonwoven fabric (having a weight per unit area of 12g/m²) was attached to the deposited surface of the support B.

Support D: A PET nonwoven fabric (having a weight per unit area of 12g/m²) was attached to one surface of the support A.

Support E: Silicon oxide was deposited from the vapor onto one surfaceof the support A so as to have a thickness of 10 nm, and then a PETnonwoven fabric (having a weight per unit area of 12 g/m²) was attachedto the deposited surface.

Support F: A PET nonwoven fabric (having a weight per unit area of 12g/m²) was attached to one surface of a PET film having a thickness of 12μm.

Support G: A PET nonwoven fabric (having a weight per unit area of 12g/m²) was attached to one surface of a PET film having a thickness of 25μm.

(Preliminary Test)

The supports D, F, and G were subjected to Evaluations a. and b. below.Table 1 below shows the results.

a. Moisture Permeability

The moisture permeability of each of the supports D, F, and G wasmeasured with a moisture-permeable cup described in JIS L1099 “method oftesting a fiber product for its moisture permeability” in conformitywith the standard by the following procedures.

(1) About 25 g of calcium chloride were weighed in themoisture-permeable cup.

(2) The support cut into a circular shape having a diameter of 70 mm wasmounted so as to be concentric with the cup.

(3) A test body was obtained by: sequentially mounting a packing made ofa synthetic resin and a metal ring on the moisture-permeable cup; fixinga side surface after the mounting with a wing nut; and sealing the sidesurface with a vinyl pressure-sensitive adhesive tape.

(4) The test body was placed in a thermo-hygrostat with its temperatureand relative humidity kept at 40±2° C. and 90±5%, respectively.

(5) After a lapse of 16 hours or more, the test body was taken out ofthe thermo-hygrostat and then its temperature was equilibrated with roomtemperature. After that, its weight was measured. The weight was definedas an initial weight (hereinafter described as “initial”).

(6) The test body was placed again in the thermo-hygrostat with itstemperature and relative humidity kept at 40±2° C. and 90±5%,respectively.

(7) After 24 hours from the procedure (6), the test body was taken outof the thermo-hygrostat and then its temperature was equilibrated withroom temperature. After that, its weight was measured. The weight wasdefined as a weight after 24 hours (hereinafter described as “24hours”).

(8) The test body was placed again in the thermo-hygrostat with itstemperature and relative humidity kept at 40±2° C. and 90±5%,respectively.

(9) After 24 hours from the procedure (8), the test body was taken outof the thermo-hygrostat and then its temperature was equilibrated withroom temperature. After that, its weight was measured. The weight wasdefined as a weight after 48 hours (hereinafter described as “48hours”).

(10) A value obtained by rounding a value calculated for each test bodyfrom the following equation to an integer value was defined as itsmoisture permeability.

Moisture permeability (g/m²⁰·24 h)=(240×m)/(txs)

-   -   s: A moisture permeation area (cm²)=28.26    -   t: The total time (h) of two weighing intervals=48    -   m: A total mass increase (mg) during the two weighing intervals

The moisture permeation area s is a value calculated from the innerdiameter of the moisture-permeable cup, i.e., 3.0 (cm) with a circleratio of 3.14. In addition, the term “weighing interval” refers to aninterval from “initial” to “24 hours” or from “24 hours” to “48 hours,”and m can be represented as described below.m=(“24 Hours”−“initial”)+(“48 hours”−“24 hours”)=“48 hours”−“initial”

Table 1 below shows the resultant moisture permeabilities.

b. Softness

The supports D, F, and G were each subjected to a softness measurementexperiment in accordance with a heart loop method specified in JIS L1096by the following procedures. Table 1 below shows the results. It shouldbe noted that a smaller value for the softness in the heart loop methodgenerally means that a sample is harder and a larger value thereforgenerally means that the sample is softer.

(1) Each support was cut into a size measuring 2 cm by 25 cm.

(2) The resultant test piece was formed into a heart loop so that itseffective length was 20 cm and its nonwoven fabric surface faced inward.Both of its ends were fixed with a pressure-sensitive adhesive tape andthen the loop was horizontally held in a state where the fixed point wasplaced upward.

(3) After a lapse of 1 minute, a distance L (mm) between the apexportion (fixed point) and the lowest point of the loop was measured to awhole digit.

(4) The procedure (3) was performed after the same procedure as theprocedure (2) except that the nonwoven fabric surface was caused to faceoutward was performed.

(5) An average was calculated from the values obtained in the procedures(3) and (4), and was defined as the softness of the support.

Reference Example 1

Under an inert gas atmosphere, 95 parts of 2-ethylhexyl acrylate, 5parts of acrylic acid, and 0.2 part of benzoyl peroxide as apolymerization initiator were compounded in ethyl acetate, and were thensubjected to solution polymerization. Thus, a solution of an acrylicpolymer A having a weight-average molecular weight of about 1,500,000was obtained. An ethyl acetate solution containing 43 parts of theacrylic polymer A as a solid content, 17 parts of isosorbide dinitrate(ISDN), and 40 parts of isopropyl myristate as an organic liquidcomponent were mixed. The mixed liquid was applied onto a PET filmhaving a thickness of 75 μm as a release liner so that its thicknessafter drying was 40 μm, followed by drying in a circulating hot airdryer at 80° C. for 5 minutes. Thus, a pressure-sensitive adhesive layerwas obtained. The pressure-sensitive adhesive layer was attached to thenonwoven fabric surface of the support D. Thus, a patch preparation wasobtained. The resultant patch preparation was subjected to Evaluationsc. to e. below. Table 1 below shows the results.

Reference Example 2

A patch preparation was obtained in the same manner as in ReferenceExample 1 except that the support F was used instead of the support D.The resultant patch preparation was subjected to Evaluations c. to e.below. Table 1 below shows the results.

Reference Example 3

A patch preparation was obtained in the same manner as in ReferenceExample 1 except that the support G was used instead of the support D.The resultant patch preparation was subjected to Evaluations c. to e.below. Table 1 below shows the results.

c. Hairless Mouse Skin Permeability Test

(1) The patch preparations of Reference Examples 1 to 3 each cut into acircular shape having a diameter of 8 mm were each released from therelease liner and then attached to the keratin surface of a skinextirpated from a hairless mouse that had been stamped into a circularshape having a diameter of 20 mm.

(2) The skin prepared in the procedure (1) was mounted on aflow-through-type diffusion cell so that the back surface of the surfaceto which the preparation had been attached contacted a receptor liquid.It should be noted that a physiological saline solution at 32° C. wasused as the receptor liquid.

(3) The receptor liquid was sampled every three hours, a drugconcentration in the sampled liquid was determined by an HPLC method,and a cumulative permeation amount (μg/cm²⁰·12 h) up to a lapse of 12hours was determined.

Further, an evaluation for drug permeability was performed by thefollowing criteria.

(Criteria)

∘: The cumulative permeation amount is larger than that of ReferenceExample 1.

x: The cumulative permeation amount is smaller than that of ReferenceExample 1.

Table 1 below shows the cumulative permeation amounts and the results ofthe evaluation for drug permeability.

d. Evaluation for Patch Feeling

The patch preparations of Reference Examples 1 to 3 each stamped into asize measuring 5 cm by 5 cm were each evaluated for its patch feelingwhen released from the release liner and attached to a skin by thefollowing criteria on the assumption that the patch preparation wasactually applied. Table 1 below shows the results.

(Criteria)

∘: There is no stiff feeling (uncomfortable feeling).

Δ: There is a weak stiff feeling (uncomfortable feeling).

x: There is a strong stiff feeling (uncomfortable feeling).

e. Evaluation for Anchoring Property

Each of the patch preparations of Reference Examples 1 to 3 was moved ina horizontal direction while a thin metal flat plate portion was lightlypressed against the pressure-sensitive adhesive layer. During that time,the presence or absence of release between the pressure-sensitiveadhesive layer and the support was visually observed, and then anevaluation for anchoring property was performed by the followingcriteria. Table 1 below shows the results.

(Criteria)

∘: No release is observed between the support and the pressure-sensitiveadhesive layer.

x: Release is observed between the support and the pressure-sensitiveadhesive layer.

TABLE 1 Reference Reference Reference Example 1 Example 2 Example 3Support Kind D F G (Base layer) 4 μm 12 μm 25 μm (Inorganic oxide — — —layer) (Nonwoven fabric Present Present Present layer) Moisture 152 5533 permeability (g/m² · 24 h) Softness (mm) 57 46 41 Patch Cumulativedrug 193 321 332 preparation permeation amount (μg/cm² · 12 h) Drugpermeability Reference ∘ ∘ Patch feeling ∘ Δ x Anchoring property ∘ ∘ ∘

As is apparent from Table 1, the moisture permeability of a supportreduces and its softness also reduces as the base layer of the supportbecomes thicker. In addition, the patch preparations of ReferenceExample 2 and Reference Example 3 have clearly larger cumulative drugpermeation amounts than that of the patch preparation of ReferenceExample 1. This shows that the use of a support having a low moisturepermeability caused a high ODT effect. On the other hand, with regard toa patch feeling, the patch preparation of Reference Example 1 was mostexcellent, the patch preparation of Reference Example 2 provided aslight uncomfortable feeling, though the feeling fell within anallowable range, and the patch preparation of Reference Example 3provided a strong uncomfortable feeling. This shows that the flexibilityof a patch preparation is insufficient when its support has a lowsoftness (that is, the support is hard). The foregoing results haverevealed that the moisture permeability can be reduced by increasing thethickness of the base layer of a support, and as a result, the drugpermeability of a patch preparation can be improved, but in such case,its flexibility reduces and hence it becomes difficult to balance thedrug permeability with the patch feeling.

Example 1

Under an inert gas atmosphere, 95 parts of 2-ethylhexyl acrylate, 5parts of acrylic acid, and 0.2 part of benzoyl peroxide as apolymerization initiator were compounded in ethyl acetate, and were thensubjected to solution polymerization. Thus, a solution of an acrylicpolymer A having a weight-average molecular weight of about 1,500,000was obtained. An ethyl acetate solution containing 43 parts of theacrylic polymer A as a solid content, 17 parts of isosorbide dinitrate(ISDN), 40 parts of isopropyl myristate as an organic liquid component,and 0.07525 part of an isocyanate-based cross-linking agent were mixed.The mixed liquid was applied onto a PET film having a thickness of 75 μmas a release liner so that its thickness after drying was 60 μm,followed by drying in a circulating hot air dryer at 80° C. for 5minutes. Thus, a pressure-sensitive adhesive layer was obtained. Thepressure-sensitive adhesive layer was attached to the nonwoven fabricsurface of the support C. Thus, a patch preparation was obtained. Theresultant patch preparation was subjected to Evaluations 1. to 6. below.Table 2 below shows the results.

Example 2

A patch preparation was obtained in the same manner as in Example 1except that the support E was used instead of the support C. Theresultant patch preparation was subjected to Evaluations 1. to 6. below.Table 2 below shows the results.

Comparative Example 1

A patch preparation was obtained in the same manner as in Example 1except that: the support A was used instead of the support C; and thepressure-sensitive adhesive layer was laminated on the PET surface. Theresultant patch preparation was subjected to Evaluations 1. to 5. below.Table 2 below shows the results.

Comparative Example 2

A patch preparation was obtained in the same manner as in Example 1except that: the support B was used instead of the support C; and thepressure-sensitive adhesive layer was laminated on the aluminumoxide-deposited surface. The resultant patch preparation was subjectedto Evaluations 1. to 6. below. Table 2 below shows the results.

Comparative Example 3

A patch preparation was obtained in the same manner as in Example 1except that: the support D was used instead of the support C; and thepressure-sensitive adhesive layer was laminated on the nonwoven fabricsurface. The resultant patch preparation was subjected to Evaluations 1.to 5. below. Table 2 below shows the results.

1. Moisture Permeability

Moisture permeability measurement was performed by using each of thepatch preparations of Examples 1 and 2, and Comparative Examples 1 to 3as an object instead of a support in the method for Evaluation a. above.At that time, the test was performed while the release liner wasremoved. Table 2 below shows the results.

2. Softness

Softness measurement was performed by the same method as the method forEvaluation b. above except the following. Each of the patch preparationsof Examples 1 and 2, and Comparative Examples 1 to 3 was used as anobject, a test piece was obtained by cutting the patch preparation intoa size measuring 1 cm by 15 cm, and a heart loop was formed so that itseffective length was 13 cm and the pressure-sensitive adhesive layerfaced inward. Table 2 below shows the results.

3. Hairless Mouse Skin Permeability Test

A hairless mouse skin permeability test was performed with each of thepatch preparations of Examples 1 and 2, and Comparative Examples 1 to 3as an object in the method for Evaluation c. above to determine acumulative permeation amount (μg/cm²⁰·12 h) up to a lapse of 12 hours.

Further, an evaluation for drug permeability was performed by thefollowing criteria.

(Criteria)

∘: The cumulative permeation amount is larger than that of ComparativeExample 3.

x: The cumulative permeation amount is smaller than that of ComparativeExample 3.

Table 2 below shows the cumulative permeation amounts and the results ofthe evaluation for drug permeability.

4. Evaluation for Handleability

The patch preparations of Examples 1 and 2, and Comparative Examples 1to 3 each stamped into a size measuring 5 cm by 5 cm were each evaluatedfor its handleability when released from the release liner and attachedto a skin by the following criteria on the assumption that the patchpreparation was actually applied. Table 2 below shows the results.

(Criteria)

∘: It is easy to attach the patch preparation to the skin withoutcausing any wrinkle.

x: It is difficult to attach the patch preparation to the skin withoutcausing any wrinkle.

5. Evaluation for Anchoring Property

An evaluation for anchoring property was performed by the same method asthe method for Evaluation e. above except that each of the patchpreparations of Examples 1 and 2, and Comparative Examples 1 to 3 wasused as an object. Table 2 below shows the results.

6. Evaluation for Durability of Inorganic Oxide Layer

Each of the patch preparations of Examples 1 and 2, and ComparativeExample 2 each using a support having an inorganic oxide layer wasrubbed by the following procedures, and then its moisture permeabilitywas measured.

(1) An area measuring 4.5 cm long by 4.5 cm wide was punched out andremoved from the central portion of a PET film which had a thickness of75 μm, and measured 10 cm long by 10 cm wide, and one surface of whichhad been subjected to a release treatment.

(2) A test body was obtained by attaching the pressure-sensitiveadhesive layer of the patch preparation released from the liner to thesurface of the PET film subjected to the release treatment so that thepatch preparation covered the entirety of the portion from which the PETfilm had been removed.

(3) A portion of the test body where the PET film and the patchpreparation were attached to each other was held by being sandwichedbetween fingers, a metal bar having a diameter of 1 cm was pressedagainst the support surface of the preparation, and the surface wasrubbed with the metal bar at a rate of one reciprocation per second 40times in a state where the test body was bent.

An evaluation for durability was performed with the moisturepermeability measured after the rubbing by the following evaluationcriteria.

(Criteria)

∘: The moisture permeability after the rubbing is smaller than themoisture permeability of Comparative Example 1.

x: The moisture permeability after the rubbing is larger than themoisture permeability of Comparative Example 1.

Table 2 below shows the moisture permeabilities after the rubbing andthe results of the evaluation for the durability of the inorganic oxidelayer.

TABLE 2 Comparative Comparative Comparative Example 1 Example 2 Example1 Example 2 Example 3 Support C E A B D (Base layer) 4 μm 4 μm 4 μm 4 μm4 μm (Inorganic oxide layer) Al₂O₃ SiO₂ — Al₂O₃ — (Nonwoven fabriclayer) Present Present — — Present Moisture permeability 20 58 111  4792 (g/m² · 24 h) Cumulative drug 304  326  252 298 264  permeationamount (μg/cm² · 12 h) Drug permeability ∘ ∘ x ∘ Reference Softness (mm)47 47  62  62 47 Handleability ∘ ∘ x x ∘ Anchoring property ∘ ∘ x x ∘Moisture permeability 58 84 — 123 — after rubbing (g/m² · 24 h)Durability of inorganic ∘ ∘ — x — oxide layer

As is apparent from Table 2, each of the patch preparations of Examples1 and 2, and Comparative Example 2, each using a support having aninorganic oxide layer, shows a lower moisture permeability and higherdrug permeability than those of each of the patch preparations ofComparative Examples 1 and 3 each using a support free of any inorganicoxide layer. Further, as a result of the combined use of the inorganicoxide layer and the nonwoven fabric layer, the extent to which themoisture permeability of the patch preparation of Example 1 reduces ismarkedly large as compared with Comparative Example 2 using theinorganic oxide layer alone and Comparative Example 3 using the nonwovenfabric layer alone. This suggests that the combined use of the inorganicoxide layer and the nonwoven fabric layer can exert a synergisticeffect. In addition, each of the patch preparations of Examples 1 and 2,and Comparative Example 3, each using a support having a nonwoven fabriclayer, shows moderate flexibility and excellent handleability. On theother hand, the patch preparations of Comparative Examples 1 and 2 eachhad so high a softness, in other words, so high flexibility as to bedifficult to attach. Further, each of the patch preparations of Examples1 and 2, and Comparative Example 3, each using a support having anonwoven fabric layer, showed excellent anchoring properties, and eachof the patch preparations of Comparative Examples 1 and 2, each using asupport free of any nonwoven fabric layer, showed insufficient anchoringproperties. Accordingly, it is found that the nonwoven fabric layer isimportant to the anchoring of the pressure-sensitive adhesive layer. Inaddition, with regard to the durability of the inorganic oxide layer,the extent to which the moisture permeability of each of the patchpreparations of Examples 1 and 2 increased after the rubbing wasmarkedly small as compared with the patch preparation of ComparativeExample 2. Accordingly, it is found that the inorganic oxide layers ofthe patch preparations of Examples 1 and 2 each have high durability.

As described above, the patch preparation according to any one of theexamples of the present invention is reduced in moisture permeability toeffectively improve the releasability of the drug while maintainingmoderate flexibility. In addition, the patch preparation can improve thedurability of the inorganic oxide layer, and can realize excellenthandleability and excellent anchoring property of the pressure-sensitiveadhesive layer.

The patch preparation of the present invention can be suitably utilizedin, for example, the transdermal administration of a drug.

Many other modifications will be apparent to and be readily practiced bythose skilled in the art without departing from the scope and spirit ofthe invention. It should therefore be understood that the scope of theappended claims is not intended to be limited by the details of thedescription but should rather be broadly construed.

What is claimed is:
 1. A patch preparation, comprising: a support; and apressure-sensitive adhesive layer containing an adherent polymer and adrug on one surface of the support, wherein: the support has a polyesterbase layer, an inorganic oxide layer, and a polyester nonwoven fabriclayer in the stated order; the polyester base layer has a thickness of1.0 μm to 16 μm, and the pressure-sensitive adhesive layer is laminatedon the polyester nonwoven fabric layer; and wherein the inorganic oxidelayer has a thickness of 1 nm to 300 nm, wherein the adherent polymercomprises an acrylic polymer obtained by copolymerizing a (meth)acrylicacid alkyl ester and a functional monomer.
 2. A patch preparationaccording to claim 1, wherein the adherent polymer comprises an acrylicpolymer obtained by copolymerizing a (meth)acrylic acid alkyl ester anda functional monomer.
 3. A patch preparation according to claim 1,wherein the pressure-sensitive adhesive layer has a thickness of 10 μmto 200 μm.
 4. A patch preparation according to claim 1, wherein thepressure-sensitive adhesive layer further contains an organic liquidcomponent.